Summary
Skeletal muscle is a complex tissue containing tissue resident muscle stem cells (satellite cells, MuSCs) important for postnatal muscle growth and regeneration. Quantitative analysis, biological function, and the molecular pathways responsible for a potential juxtavascular niche for MuSCs is currently lacking. We utilized fluorescent reporter mice and muscle tissue clearing to investigate the proximity of MuSCs to capillaries in 3-dimensions. We show that MuSCs express abundant VEGFA, which recruits endothelial cells (ECs) in vitro, whereas both blocking VEGFA by a VEGF inhibitor and MuSC-specific VEGFA gene deletion reduce the proximity of MuSCs to capillaries. Importantly, this proximity to the blood vessels was associated with MuSC self-renewal in which EC-derived Notch ligand Dll4 induces quiescence in MuSCs. We hypothesize that MuSCs recruit capillary ECs via VEGFA, and in return ECs maintain MuSC quiescence though Dll4.
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